For a rational approach to the development and use of antineoplastic drugs we need to know their biochemical effects on cells, and the relation of those effects to cell survival. In particular such information may now be useful for the haloethyl nitrosoureas, compounds that are especially promising because of their high degree of activity against a broad spectrum of tumor types. All the nitrosoureas have alkylating activity; most have carbamoylating activity. The latter is not essential for antitumor activity, and may or may not augment the cytotoxicity produced by alkylation. This study is aimed at answering the question of whether any of the potentially lethal biochemical effects caused by the carbamoylating activity of nitrosoureas are correlated with cytotoxicity. Cell cultures treated with either weakly or strongly carbamoylating nitrosoureas will be compared for: a) patterns of inhibition of synthesis of DNA, RNA, and protein; (b) inhibition of RNA processing; and c) inhibition of DNA repair (rejoining of X-ray-induced single-strand breaks). The correlation between each of these effects and cytotoxicity will be examined for both types of drug. The reported synergism of nitrosoureas for conventional alkylating agents (seen in animal studies) may relate to their carbamoylating activity. To study this question, strongly carbamoylating nitrosoureas will be examined for synergism (more-than-additive cytotoxicity for cultured cells) with alkylating agents. If synergism is found, weakly carbamoylating drug will be substituted, to see whether synergism is maintained or lost. Results indicating that carbamoylation is unimportant to antitumor activity would point toward development of weakly carbamoylating nitrosoureas for clinical use, since carbamoylation is a likely source of host toxicity. Results indicating that carbamoylation augments antitumor activity would prompt a search for carbamoylating agents (isocyanates, formed in the decomposition of nitrosoureas) having some selectivity in their reactions with proteins.